Lab-on-a-Chip Made of Paper

Lab-on-a-Chip Made of Paper

Color coding: This prototype of a new paper diagnostic test from Harvard University analyzes the glucose (left well) and protein (right well) content of urine; the top well is a control for the glucose assay. The beige part of the test paper has been treated with a hydrophobic polymer that channels the liquid into the wells. In this test, the paper was dipped in an artificial urine solution that contained glucose and a protein extracted from cow blood.

By taking advantage of the natural movement of liquid through paper, researchers at Harvard’s Whitesides Research Group may have found a way to make microfluidics technology much cheaper. The result could be disposable diagnostic tests simple and abundant enough for use in the developing world.

The field of microfluidics deals with the precise manipulation of tiny quantities of liquid. One of its most promising applications is the so-called lab-on-a-chip, which can work with much smaller fluid samples than larger devices require, potentially allowing for more portable diagnostic tools. But existing microfluidic chips are generally made from comparatively expensive materials like silicon, glass, or plastic and have tiny pumps and valves that can be difficult to manufacture.

Now, Harvard’s George Whitesides and his team have built a microfluidic device on a square of paper the size of a pinky fingernail. “It’s the first example I’ve heard of paper microfluidics,” says Albert Folch, a bioengineer at the University of Washington who works on microfabrication. “It’s really clever because it uses paper as a substrate, which is universally available.”

While larger paper tests (like those for pregnancy) are common, shrinking the paper and minimizing the quantity of the required chemical reagents reduces manufacturing costs. The ability to direct the sample to particular regions of the paper enables the simultaneous performance of several tests, to look for multiple symptoms of a condition, like kidney failure or infectious disease, says Whitesides. And reducing sample size is a particular advantage in developing countries, where noninvasively gathering small amounts of fluids avoids the need for syringes, which can be hard to clean and dispose of.

A pinprick of blood or drop of urine soaked up at the edge of the Whitesides device moves naturally through the paper, in much the way that wine will spread through a paper napkin. But the paper is treated with a hydrophobic polymer, which directs the liquid along prescribed channels. Once the liquid reaches the wells at the ends of the channels, it interacts with reagents, turning the paper different colors. The colors can be matched to those on a color key, much as they are in a pH test. One test design that looks like a miniature, three-branched, geometric tree might have wells at the end of two branches for a glucose assay and one at the end of the third for a protein assay, for example.

The design dispenses with expensive components common in conventional microfluidic devices: chemical reactions that color parts of the paper replace sophisticated sensors and analyzers, while using paper’s natural capillary action to absorb liquids avoids the need for external pumps or power sources. Diagnostic for All–a spinoff cofounded by Whitesides and Harvard visiting scholar Hayat Sindi, with the support of partners from MIT–is commercializing the technology.

Instead of etching channels into a material, as most microfluidics designers do, Whitesides and Sindi were able to take advantage of the network of channels inherent in paper; the hydrophobic polymer simply seals off the channels that the researchers don’t want to use. “What’s really clever about this system is that they’ve actually patterned the whole volume of the substrate,” Folch explains. “The paper itself forms a network of capillaries.”